We are continuing to study the role of autoimmunity in the pathogenesis of certain central nervous system disorders. Specifically, we are screening the sera and/or cerebrospinal fluid of patients affected by Stiff-Man syndrome (SMS) for the presence of autoantibodies directed against central nervous system antigens (such as glutamin acid decarboxylase (GAD) and amphiphysin). In the past year , we have tested an additional 74 subjects. Of these, 15 have been found to display high titre autoantibodies to either GAD or amphiphysin. We are further investigating these cases since we have found a link in SMS patients between the presence of GAD autoantibodies and the onset of insulin dependent diabetes mellitus (IDDM) and also a link between the presence of amphiphysin autoantibodies and the occurrence of breast cancer. We plan to continue these studies since they may lead to the development of diagnostic tools for SMS, IDDM and breast cancer.